Connective tissue prosthesis

ABSTRACT

A semi-bioabsorbable connective tissue prosthesis, e.g., a replacement for the human anterior cruciate ligament, is provided whose stress-strain characteristics closely match those of the natural tissue.

CROSS REFERENCE TO RELATED APPLICATION

The application is a continuation-in-part of commonly assigned,co-pending U.S. patent application Ser. No. 349,648, filed May 10, 1989,now U.S. Pat. No. 4,990,158.

BACKGROUND OF THE INVENTION

This invention relates to a connective tissue prosthesis and, inparticular, to a biocompatible ligament or tendon prosthesis whichclosely approximates the biomechanical characteristics of the naturaltissue to be replaced or augmented.

Numerous connective tissue materials and constructions have beenproposed for use as temporary or permanent grafts in ligament and tendonrepair. Feagin, Jr., Ed., The Crucial Ligaments/Diagnosis and Treatmentof Ligamentous Injuries About the Knee (Churchhill Livingstone, N.Y.,1988) describes a number of partially bioabsorbable materials which havebeen investigated for use as ligament grafts. In Chapter 33 of thispublication (Rodkey, "Laboratory Studies of Biodegradable materials forCruciate Ligament Reconstruction"), it is reported that while a 100percent biodegradable ligament fabricated from polyglycolic acid (PGA)was found to be safe, strong, well-tolerated and provided stability forthe repaired anterior cruciate ligament in dogs, its complete resorptionwithin five weeks makes it unsuitable for use in prostheses intended forhumans since a human ligament prosthesis must provide support over amuch longer period of time. It is further reported that a study in dogsof the intraarticular use of a partially biodegradable ligamentprosthesis possessing a Dacron (i.e., DuPont's polyethyleneterephthalate (PET)) and PGA core and a separate outer sleeve woven fromPGA and Dacron of a different percentage of composition gavedisappointing results.

U.S. Pat. Nos. 4,792,336 and 4,942,875 describe a surgical device forrepairing or augmenting connective tissue and comprising a plurality offibers, in which the majority of the fibers are in a directionessentially parallel to the length of the device and can be either 100percent bioabsorbable or can contain a nonabsorbable component.Additionally, sleeve yarns consisting completely of absorbable materialwrap around these axial or warp yarns.

Biomedical Business International Report No. 7041 (Second Revision, May1986), "Orthopaedic and Diagnostic Devices", pages 5--5 to 5-12,identifies a variety of materials which have been used in thefabrication of prosthetic ligaments including carbon fiber, expandedTeflon (i.e., DuPont's polytetrafluoroethylene), a combination ofsilicone and PET, polypropylene, polyethylene, nickel-chromium alloyfibers individually enclosed in synthetic textile or natural silk,carbon material coated with gelatin, polyester combined with PET fibers,bovine tissues, and others.

Other disclosures of ligament and tendon repair devices are provided,inter alia, in U.S. Pat. Nos. 3,805,300; 4,187,558; 4,301,551;4,483,023; 4,584,722; 4,610,688; 4,668,233; 4,775,380; 4,788,979; andPCT Patent Publication No. WO 89/01320.

Chapter 33 (page 540) of the Feagin, Jr. publication referred to aboveidentifies the characteristics of an ideal ligament prosthesis asfollows:

(1) it must be durable with adequate strength to withstand the extremeforces placed upon it, yet compliant enough to allow for repetitivemotion without failure or excessive creep elongation;

(2) it must be tolerated by the host with no antigenic or carcinogenicreaction;

(3) if partially or completely biodegradable, the size of the individualfibers and the construction pattern must be appropriate to support andallow eventual reconstitution of the repaired structure with ingrowth offibrous tissue that matures to normal or near normal collagen;

(4) it must tolerate sterilization and storage; and

(5) it should be easily implanted using surgical and potentiallyarthroscopic techniques.

The existence of so many different types of materials and devices foruse in connective tissue repair, some of which have been identifiedabove, bears testimony to the difficulty of meeting some, much less all,of the foregoing characteristics in a single prosthetic device.

SUMMARY OF THE INVENTION

It is a principal object of the invention to provide asemi-bioabsorbable or fully bioabsorbable connective tissue prosthesis,e.g., a ligament or tendon repair device, which exhibits thestress-strain properties of the natural tissue to be replaced oraugmented.

It is a specific object of the invention to provide the foregoingconnective tissue prosthesis as a structure formed from a composite yarncomprising a non-bioabsorbable core yarn surrounded by a bioabsorbableor semi-bioabsorbable cover or sheath yarn.

It is a further specific object of the invention to provide a connectivetissue prosthesis formed from a composite yarn wherein an elastic coreyarn is wrapped with a relatively inelastic, bioabsorbable orsemi-bioabsorbable sheath yarn, so as to exhibit the stress-strainproperties of natural tissue.

It is another specific object of the invention to provide a prostheticreplacement for a human anterior cruciate ligament which is based on theaforesaid structure, in particular, one fabricated from a yarn whosesheath yarn component is derived from a glycolide-lactide copolymer.

In keeping with these and other objects of the invention, there isprovided a connective tissue prosthesis comprising:

(a) a core made up of a first biocompatible composite yarn extending inthe lengthwise direction; and

(b) a sheath surrounding the core and fabricated from a secondbiocompatible yarn,

wherein the first composite yarn in the core (a) comprises abiocompatible, non-bioabsorbable core yarn component surrounded by abiocompatible, bioabsorbable or semi-bioabsorbable sheath yarncomponent.

The second biocompatible yarn forming the sheath (b) may be the same as,or different from, the first composite yarn which forms the core (a).More specifically, the second biocompatible yarn may also comprise abiocompatible, non-bioabsorbable core yarn component surrounded by abiocompatible, bioabsorbable or semibioabsorbable sheath yarn component.

Also in keeping with the above and other objects of the invention, aconnective tissue prosthesis is provided which comprises a tubularcomponent fabricated from composite yarn, the yarn comprising abiocompatible, nonbioabsorbable core yarn component surrounded by abiocompatible, bioabsorbable or semi-bioabsorbable sheath yarncomponent.

The foregoing connective tissue prostheses meet the Feagin, Jr.criteria, identified sucra, to a surprising degree. Due to elasticity ofthe composite yarn core component and relative inelasticity of thecomposite yarn sheath component, the stress-strain characteristics ofthe connective tissue prostheses closely match those of the naturaltissue which they replace and their resorption properties can becalibrated to maintain the functionality of the prostheses throughoutthe entire period of the tissue regeneration process. The prostheses ofthis invention are readily sterilizable, possess good storage stabilitywhen suitably protected from hydrolytic forces, and can be installed ata ligament, tendon, vascular, or tracheal repair site employing knownsurgical reconstruction techniques.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 and 2 are enlarged isometric views of composite yarns which areutilized in the construction of the connective tissue prosthesis herein;

FIG. 3 is an enlarged isometric view of an alternative composite yarnutilized in the construction of the connective tissue prosthesis herein;

FIG. 4 is a schematic, cross-sectional view along line 4--4 of FIG. 3;

FIG. 5 represents a section of a ligament prosthesis manufactured fromthe composite yarn of FIG. 1 and suitable for use in the surgicalreconstruction of the human anterior cruciate ligament;

FIG. 6 is a plot of experimental data showing the stress-straincharacteristics of the prosthesis of FIG. 5 compared with thestress-strain characteristics of a natural ligament as reported in theliterature;

FIG. 7 represents a section of a tubular ligament prosthesismanufactured from the composite yarn of the present invention and havingan unbraided center section;

FIG. 8 represents a section of a tubular ligament prosthesis similar toFIG. 7 and additionally having the unbraided center section helicallywrapped with a yarn;

FIG. 9 represents a section of a braided prosthesis manufactured fromcomposite yarn of the present invention and modified in various fashionover the length thereof;

FIG. 10 represents a section of a tubular braided prosthesismanufactured from composite yarn of the present invention and providedwith threading means;

FIG. 11 represents a section of a prosthesis manufactured from compositeyarn of the present invention in which the prosthesis is branched; and

FIG. 12 is a plot of experimental data showing the stress-straincharacteristics of the prosthesis of FIG. 7 compared with a caninepatellar tendon.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

As shown in FIG. 1, composite yarn 10 comprises a core yarn component 12made up of a multiplicity of individual biocompatible, essentiallynon-bioabsorbable and preferably elastic filaments 13, advantageouslyprovided with a slight to moderate twist, and a sheath yarn component 14made up of a multiplicity of individual biocompatible, bioabsorbable orsemi-bioabsorbable and preferably relatively inelastic filaments 15wound in a first direction around the core and an externalmultifilamentous sheath yarn component 16, also made up of individualbiocompatible, bioabsorbable or semi-bioabsorbable and preferablyrelatively inelastic filaments 17, wound in a second and oppositedirection around sheath yarn component 14. For example, multifilamentoussheath yarn component 16 may comprise both absorbable and non-absorbablefilaments 17. Generally, the filaments 13 of core yarn component 12 aresubstantially parallel.

Non-bioabsorbable core yarn component 12 functions to impart elasticityto composite yarn 10 and acts as a scaffolding during and afterabsorption of the bioabsorbable sheath. Bioabsorbable sheath yarncomponents 14 and 16 function to provide the composite yarn withrelative inelasticity, tensile strength, and absorption characteristicswhich allow for desirable tissue in-growth and incorporation of thecomposite yarn into the body structure. Sheath yarn components 14 and 16each have a lengthwise axis which is non-perpendicular to the lengthwiseaxis of core component 12. While core yarn component 12 can be wrappedwith a single layer of sheath yarn component, the illustratedarrangement of two layers of sheath yarn components 14 and 16 isgenerally preferred as this construction helps to give composite yarn 10a balanced structure which resists crimping or kinking when used in themanufacture of a prosthesis such as shown in FIGS. 5 and 7-11.

Where, as shown in the embodiment of FIG. 1, at least two sheath yarncomponents are employed in the construction of the composite yarn, thecomposition, number and denier of the individual filaments, and braiding(if any) of these yarn components as well as their relative rates ofbioabsorption can differ. For example, non-absorbable filaments may becombined with absorbable filaments to provide one or moresemi-absorbable sheath yarn components. This capability for differentialabsorption can be advantageously exploited in a connective tissueprosthetic device in which the outermost sheath yarn component isabsorbed by the body at a faster rate than the underlying sheath yarncomponent, or vice versa. thus resulting in a staged absorption of thesheath components of the composite yarn.

Core yarn component 12 must be essentially non-bioabsorbable, i.e., itmust resist degradation when, as part of the connective tissueprosthesis of this invention, it is implanted in a body. The term"non-bioabsorbable" as used herein applies to materials whichpermanently remain within the body or at least remain in the body for arelatively long period of time, e.g., at least about two years. It ispreferred to employ a core yarn material which is also elastic, i.e, apolymeric material which in filamentous form exhibits a relatively highdegree of reversible extensibility, e.g., an elongation at break of atleast about 30 percent, preferably at least about 40 percent and morepreferably at least about 50 percent. Fiber-forming polymers which areboth non-bioabsorbable and elastic, and as such preferred for use as thecore yarn component herein, include fiber-forming polyolefins such aspolyethylene homopolymers, polypropylene homopolymers, ethylenepropylene copolymers, ethylene propylene terpolymers, etc., fluorinatedhydrocarbons, fluorosilicones, isobutylenes, isoprenes, polyacrylates,polybutadienes, polyurethanes, polyether-polyester copolymers, and thelike. Hytrel (DuPont), a family of copolyester elastomers based on(soft) polyether segments and (hard) polyester segments, and spandex, anelastomeric segmented polyurethane, provide especially good results.

Hytrel is manufactured in various commercial grades by DuPont, such asHytrel 4056, 5526, 5556 and 7246. Hytrel 5556 is especially suitable asthe core component 12 of the composite yarn 10 when used to form avascular graft, while Hytrel 7246 is well-suited for the core component12 of the composite yarn 10 when used to form a ligament prosthesis ortendon augmentation device.

Several properties of the various Hytrel grades are presented in thetable below:

    __________________________________________________________________________                     Hytrel Grade No.                                                              (Injection Molded at 23° C. for Testing)                               4056  5526  5556  7246                                       __________________________________________________________________________    Hardness in durometer                                                                          40    55    55    72                                         points (ASTM Test No. D2240)                                                  Flexural Modulus                                                              (ASTM Test No. D790)                                                          at -40° C. in MPa                                                                       155   930   930   2,410                                      at -40° F. in psi                                                                       22,500                                                                              135,000                                                                             135,000                                                                             350,000                                    at 23° C. in MPa                                                                        55    207   207   518                                        at 73° F. in psi                                                                        8,000 30,000                                                                              30,000                                                                              75,000                                     at 100° C. in MPa                                                                       27    110   110   207                                        at 212° F. in psi                                                                       3,900 16,000                                                                              16,000                                                                              30,000                                     ASTM Test No. D638                                                            .sup.(i) Tensile Strength at Break,                                           MPa              28.0  40.0  40.0  45.8                                       psi              4050  5800  5800  6650                                       .sup.(i) Elongation at Break, %                                                                550   500   500   350                                        .sup.(ii) Tensile Stress at 5% Strain,                                        MPa              2.4   6.9   6.9   14.0                                       psi              350   1,000 1,000 2,025                                      .sup.(ii) Tensile Stress at 10% Strain,                                       Mpa              3.6   10.3  10.3  20.0                                       psi              525   1,500 1,500 2,900                                      Izod Impact (Notched) (ASTM                                                   Test No. D256, Method A)                                                      at -40° C. in J/cm                                                                      No Break                                                                            No Break                                                                            No Break                                                                            0.4                                        at -40° F. in ft-lbf/in                                                                 No Break                                                                            No Break                                                                            No Break                                                                            0.8                                        at 23° C. in J/cm                                                                       No Break                                                                            No Break                                                                            No Break                                                                            2.1                                        at 73° F. in ft-lbf/in.                                                                 No Break                                                                            No Break                                                                            No Break                                                                            3.9                                        Resistance to Flex Cut Growth,                                                                 >1 × 10.sup.6                                                                 >5 × 10.sup.5                                                                 >5 × 10.sup.5                                                                 --                                         Ross (Pierced), in Cycles to 100%                                             cut growth (ASTM. Test                                                        No. D1052)                                                                    .sup.(iii) Initial Tear Resistance, Die C                                     (ASTM Test No. D1004),                                                        in kN/m          101   158   158   200                                        in lbf/in.       580   900   900   1,146                                      Melt Flow Rate in g/10 min.                                                                    5.3   18    7.0   12.5                                       (ASTM Test No. D1238)                                                         Test Conditions: Temperature,                                                                  190/2.16                                                                            220/2.16                                                                            220/2.16                                                                            240/2.16                                   °C./Load, Kg                                                           .sup.(iv) Melting Point (ASTM Test No.                                        D3418)                                                                        in °C.    148   202   202   219                                        in °F.    298   396   396   426                                        Vicat Softening Point (ASTM Test                                              No. D1525)                                                                    in °C.    108   180   180   207                                        in °F.    226   356   356   405                                        Specific Gravity (ASTM Test                                                                    1.16  1.20  1.20  1.25                                       No. D792)                                                                     Water Absorption, 24 hr. in %                                                                  0.6   0.5   0.5   0.3                                        (ASTM Test No. D570)                                                          __________________________________________________________________________     .sup.(i) head speed 50 mm/min. or 2 in/min.                                   .sup.(ii) head speed 25 mm/min. or 1 in/min.                                  .sup.(iii) specimens 1.9 mm or 0.075 in. thick.                               .sup.(iv) differential scanning calorimeter (DSC), peak of endotherm     

Corresponding properties of other grades of Hytrel are available fromDuPont.

If desired, the core yarn component can be provided with a nonabsorbablehydrophilic coating to improve its wettability by body fluids, e.g.,synovial fluid. Hydrophilic coatings which are suitable for this purposeinclude polymeric materials such as the sparingly crosslinkedpoly(hydroxyethyl methacrylate) hydrogels disclosed in U.S. Pat. Nos.2,976,576 and 3,220,960; hydrogels based on cross-linked polymers ofn-vinyl lactams and alkyl acrylates as disclosed in U.S. Pat. No.3,532,679; graft copolymers of hydroxyalkyl methacrylate andpolyvinylpyrrolidone disclosed in U.S. Pat. No. 3,621,079, and manyothers.

Fiber-forming materials which are relatively inelastic are suitable forproviding the sheath yarn component of composite yarn 10 provided suchmaterials are fairly rapidly bioabsorbed by the body, e.g., exhibiting aloss of tensile strength in from about 2 to about 26 weeks and totalabsorption within from about two to about fifty two weeks. It is to beunderstood, however, that the expression "relatively inelastic" does notpreclude the presence of some minor degree of elasticity in the sheathyarn component, merely that it excludes a degree of elastic behavior asdescribed in connection with the preferred type of core yarn component.

The sheath yarn component can be woven, braided or knitted in whole orin part and will ordinarily possess a relatively high tensile strength,e.g., a straight tensile strength of at least about 30,000 p.s.i.,preferably at least about 60,000 p.s.i. and more preferably at leastabout 90,000 p.s.i.

Bioabsorbable, relatively inelastic fiber-forming polymers and polymerblends from which the sheath yarn component herein can be formed includethose derived at least in part from such monomers as glycolic acid,glycolide, lactic acid, lactide, p-dioxanone, trimethylene carbonate,e-caprolactone, hydroxycaproic acid, etc., and various combinations ofthese and related monomers as disclosed, e.g., in U.S. Pat. Nos.2,668,162; 2,703,316; 2,758,987; 3,225,766; 3,297,033; 3,422,181;3,531,561; 3,565,077; 3,565,869; 3,620,218; 3,626,948; 3,636,956;3,736,646; 3,772,420; 3,773,919; 3,792,010; 3,797,499; 3,839,297;3,867,190; 3,878,284; 3,982,543; 4,047,533; 4,052,988; 4,060,089;4,137,921; 4,157,437; 4,234,775; 4,237,920; 4,300,565; 4,429,080;4,441,496; 4,523,591; 4,546,152; 4,559,945; 4,643,191; 4,646,741;4,653,497; and, 4,741,337; U.K. Patent No. 779,291; D. K. Gilding etal., "Biodegradable polymers for use insurgery--polyglycolide/poly(lactic acid) homo- and copolymers: 1",Polymer, Volume 20, pages 1459-1464 (1979), and D. F. Williams (ed.),Biocompatibility of Clinical Implant Materials, Vol. II, ch. 9:"Biodegradable Polymers" (1981).

Sheath yarn components manufactured from polymers of high lactide orglycolide content, e.g., those in which at least about 75 percent of themonomeric units are derived from either glycolide or lactide, arepreferred for the construction of the composite yarn of this invention.Polymers of high glycolide content tend to be absorbed more quickly thanthose possessing a high lactide content. Accordingly, theglycolide-based polymers may be preferred for the manufacture of asheath yarn component providing the outermost sheath yarn(s) in amultiple sheath yarn component construction, the underlying internalsheath yarn(s) being manufactured from the more slowly absorbablelactide-based polymers. An especially preferred lactide-glycolidecopolymer for forming the sheath yarn component of the composite yarncontains from about 70 to about 90, and preferably from about 75 toabout 85 mole percent lactide monomer with the balance being provided bythe glycolide monomer. Thus, for example, a sheath yarn component formedfrom a lactide-glycolide copolymer based on 80 mole percent lactide-20mole percent glycolide is especially advantageous for constructing thecomposite yarn, and ultimately, the connective tissue prosthesis, of thepresent invention. The sheath yarn component, which is preferablybraided around the core yarn component, may comprise a plurality ofbioabsorbable fibers in turn comprising at least two different chemicalcompositions.

The deniers of core yarn component 12 and sheath yarn components 14 and16 are not especially critical and those of commercially available yarnssuch as Vicryl (a glycolide/lactide copolymer suture available fromEthicon) and Dexon (a polyglycolide suture available from AmericanCyanamid) are suitably employed. Preferably, the deniers are selected soas to provide a composite yarn having an overall denier of from about 40to about 1200 and preferably from about 80 to about 500, the overalldenier of the core and/or sheath yarn components being from about 20 toabout 600 and preferably from about 40 to about 300. The deniers ofindividual filaments in the core and sheath yarn components ofmultifilamentous construction can vary widely, e.g., from about 0.2 toabout 6.0 and preferably from about 0.4 to about 3.0. The base weightfor a desired composite yarn will determine the size and weight of thecomponent elements of the yarn. Composite yarn 10 possesses sufficientcore material to impart, inter alia, a desired resiliency and sufficientsheath material to provide, inter alia. a desired tensile strength for aparticular connective tissue prosthetic application. In general, thecore component can represent from about 20 to about 80 percent, andpreferably from about 30 to about 70 percent of the total weight ofcomposite yarn 10. Optimum core and sheath component weights willnaturally vary depending on the specific application and can be readilydetermined in a given case based on the desired physical properties ofthe prosthetic device without undue experimentation.

Methods and apparatus for covering core yarn components with sheath yarncomponents are well known and need not be described here in detail. Ingeneral, the sheath yarn components are wrapped about the core yarncomponent on a covering machine which includes a hollow spindle withrotating yarn supply bobbins supported thereon. The elastic core yarncomponent is fed through the hollow spindle and the elastic sheath yarncomponents are withdrawn from the alternate direction rotating supplybobbins and wrapped about the core yarn component as it emerges from thehollow spindle. The core yarn component is preferably under a slighttension during the covering procedure and the sheath yarn components arelaid down in a side-by-side array. The number of wraps per inch willdepend on the denier of the sheath yarn components but should besufficient to cause the sheath yarn components to lay close to the coreyarn component when tension on the latter is relaxed.

As desired, the filaments which comprise a sheath yarn component can beprovided with no twist or with varying degrees of twist. Where the yarnsare twisted, it can be advantageous to balance or equalize the twist inthe final composite yarn structure. Thus, for example, in the embodimentof composite yarn 10 in FIG. 1, if sheath yarn component 14 has a giventwist, sheath yarn component 16 should have an equivalent twist. Sincesheath yarn components 14 and 16 are laid down in opposite directions,the twist in each of these yarn components will be neutralized in thefinal structure of the composite yarn. Similarly, sheath yarn components14 and 16 are advantageously of about equal weight in order to providefurther balance in the composite yarn.

The composite yarn 20 shown in FIG. 2 is similar to that of FIG. 1except that core yarn component 22 constitutes a monofilament andinternal and external sheath yarn components 24 and 26, respectively,each constitutes a monofilament. In all other structural andcompositional respects, composite yarn 20 can be like that of compositeyarn 10.

An alternative composite yarn 30 is illustrated in FIGS. 3 and 4.Composite yarn 30 comprises a core yarn component 33 and a braidedsheath yarn component 34. As with core yarn components 12 and 22 ofFIGS. 1 and 2, core yarn component 33 is made up of one or morebiocompatible, essentially non-bioabsorbable and preferably elasticfilaments 36 which define the longitudinal axis of composite yarn 30.Braided sheath yarn component 34 comprises individual sheath yarnfilaments or sheath yarn filament bundles 35 which traverse core yarncomponent 33 in a substantially conventional braided configuration toprovide core yarn component 33 with a braided tubular external sheath34. The individual sheath yarn filaments or sheath yarn filament bundles35 are biocompatible, bioabsorbable or semi-bioabsorbable, andrelatively inelastic. In a preferred embodiment of the present inventionas illustrated in FIGS. 3 and 4, sheath yarn component 34 comprisessheath yarn filaments of different chemical composition. For example, aportion of the sheath yarn filaments 35', e.g., 30 to 70% by weight, maybe formed of a bioabsorbable polymer exhibiting relatively slowbioabsorption, e.g., polylactide or a copolymer comprising a highlactide mole percentage, while the remainder of the sheath yarnfilaments 35" may be formed of a second bioabsorbable polymer whichexhibits relatively fast bioabsorption, e.g., polyglycolide or acopolymer comprising a high glycolide mole percentage. Sheath yarncomponent 34 may also be fabricated from individual filaments havingmore than two different chemical compositions, one or more of whichoptionally being nonbioabsorbable.

In the embodiment illustrated in FIGS. 3 and 4, core yarn component 33is preferably manufactured from Hytrel filaments 36 and has a denier ofabout 270, while sheath yarn component 34, which is braided on an eightcarrier braider, has a denier of about 204, for a total denier of thiscomposite yarn 30 of about 474.

FIG. 5 illustrates an anterior cruciate ligament prosthesis 37manufactured from warp and filling composite yarns 10 of FIG. 1.Prosthesis 37 is constructed by constructing a sheath 31 about core 32by weaving, braiding or knitting on a known or conventional loom. Forexample, the sheath may be braided about the core on a braiding machinewhich includes braider bobbins. Composite yarn forming the sheath may bewound onto an appropriate number of braider bobbins which are thenloaded onto a carrier braider with the yarns on the bobbins then beingbraided and tied to form the sheath. The core (if one is required) canbe pulled through the sheath, e.g. manually to form the prosthesis. Inother words, the core will be at least partially surrounded by thesheath. Other prostheses illustrated herein can be manufactured insimilar fashion. The sheath components of the individual composite yarnsfrom which ligament prosthesis 30 is manufactured will erode over timedue to their bioabsorption leaving only the nonabsorbable core componentas a permanent or long term scaffold for new ligament tissue growth.

FIGS. 7-11 illustrate examples of other ligament prostheses which can bemanufactured from the composite yarn of the present invention, e.g. asillustrated in FIGS. 1-3. More particularly, FIG. 7 illustrates atubular ligament prosthesis or tendon augmentation device 40 having anunbraided center section 41 bounded by braided sections 42 and 43. Theindividual composite yarns 44 in the unbraided center section 41 can bedrawn in generally parallel relationship, if required. The length of theunbraided center section 41 can vary, e.g., from about one or two inchesup to about seven or eight inches. The unbraided center section 41provides tensile strength and/or tissue ingrowth advantages.

Additionally, a tubular ligament prosthesis or tendon augmentationdevice 45 as illustrated in FIG. 8 can be manufactured from thecomposite yarn of the present invention. The prosthesis 45 is similar tothe one illustrated in FIG. 7 and comprises an unbraided center section46 bounded by braided sections 47 and 48. A helical wrap 100 is providedabout the unbraided center section 46 to improve handling andmanipulation of the unbraided section 46 during implantation, whileabsorption/degradation of the helical wrap 100 frees the individualyarns 49 of the center unbraided section 46 to provide the appropriatetensile strength and/or tissue ingrowth advantages. In this regard, theyarn forming the helical wrap 100 can be the composite yarn of FIGS. 1-3or formed of a different kind of material, e.g. completely bioabsorbableor nonbioabsorbable material. The tubular ligament prostheses of FIGS. 7and 8 are both constructed by braiding the end sections 42, 43 or 47, 48in a known or conventional loom and, in the case of FIG. 8, additionallywrapping the helical yarn 100 about the center unbraided section 46,also with a known or conventional loom. The prostheses of FIGS. 7 and 8are especially suitable as replacements for anterior cruciate ligaments.

FIG. 9 illustrates a braided prosthesis 70 which can be manufacturedfrom the composite yarns of FIGS. 1-3 and which is also modified alongthe length thereof. More specifically, the prosthesis of FIG. 9comprises a center region 50 bordered by first outer regions 51, 52,second outer regions 53, 54, third outer regions 55, 56, fourth outerregions 57, 58, and fifth outer regions 59, 60. The center region 50comprises a sheath of braided composite yarn, e.g., as illustrated inFIGS. 1-3, about a core (not illustrated) also formed of composite yarn.First outer regions 51, 52 additionally comprise a wrapping 61 about thebraided yarn, this wrapping 61 being formed of the same composite yarnas illustrated in FIGS. 1-3 or a different kind of material, e.g. atotally bioabsorbable or nonabsorbable material. This wrapping 61 servesto at least temporarily retain the sheath about the core.

The second outer regions 53, 54 also formed of tubular braided compositeyarn as illustrated in FIGS. 1-3 with an appropriate core material (notillustrated) that forms a thicker core than any core present in centersection 50 (the center section 50 can be coreless, if required). Thirdouter regions 55, 56 are divided as illustrated in FIG. 9 to formrespective openings 62 and 63. This allows attachment means to beinserted through the respective openings to secure the ligamentprosthesis 70 in place. As illustrated in FIG. 9, the sections 55, 56around the openings 62 and 63 are also covered with wrapping 64 which issimilar to the wrapping 61 covering regions 51 and 52.

Next, fourth outer regions 57 and 58 follow which are similar instructure and composition to second outer regions 53 and 54. Regions 57and 58 narrow down into fifth outer regions 59 and 60 as illustrated inFIG. 9, which can be used, e.g. for threading the ligament prosthesis70. All sections of prosthesis 70, including the various wrappings 61and 64, can be fabricated together on a conventional known loom.Prosthesis 70 is especially suitable as a replacement for an anteriorcruciate ligament.

FIG. 10 discloses a coreless prosthetic ligament 80 that can be preparedfrom the composite yarn illustrated in FIGS. 1-3. The corelessprosthetic ligament is braided with a wider central section 81, and anarrower outer section from which unwoven yarns 83 extend to form aleading section to enhance threading of prosthetic ligament 80 uponimplantation. Sheath yarns 84 of prosthetic ligament 80 can be woven,braided, or knitted on a conventional loom. Sheath sections 81 and 82 ofligament prostheses 80 are tubular, i.e. coreless. Prostheses 80 is alsoespecially suitable as a replacement for an anterior cruciate ligament.

As illustrated in FIG. 11, a ligament prosthesis 90 can be prepared fromcomposite yarns illustrated in Figs. 1-3 of the present invention whichform a sheath about a supporting structure (not illustrated). Thissupporting structure can be a core formed from the composite yarns asdescribed above, or it can be a single, integral member, formed ofsemi-bioabsorbable or non-bioabsorbable material forming a supportingbase for yarns 91. This supporting structure, along with the bundle ofyarns 91, can be divided into two branches 90a and 90b, with the yarns91 of the prosthesis retained on the supporting structure or core atvarious points by fastening means 92 which can also be constituted bycomposite yarn of FIGS. 1-3 or by other kinds of material, e.g. totallybioabsorbable or nonabsorbable filaments. In this regard, the yarns 91need just be bundled together without any interweaving, braiding orknitting, so long as the yarns 91 are securely held together on the coreby the fastening means 92. Alternatively, yarns 92 can be woven,knitted, or braided about the core on a conventional loom to formbranches 90a and 90b.

Other prosthetic structures which can be prepared with the compositeyarn of the present invention are apparent to one of skill in the art inlight of the disclosure herein.

It is within the scope of this invention to coat or impregnate theprosthesis with, or otherwise apply thereto, one or more materials whichenhance its functionality, e.g., surgically useful substances, such asthose which accelerate or beneficially modify the healing process whenthe prosthesis is applied to a graft site. So, for example, theprosthesis can be provided with a therapeutic agent which will bedeposited at the grafted site. The therapeutic agent can be chosen forits antimicrobial properties, capability for promoting tissue repair orfor specific indications such as thrombosis. Thus, for example,antimicrobial agents such as broad spectrum antibiotics (gentamicinsulphate, erythromycin or derivatized glycopeptides) which are slowlyreleased into the tissue can be incorporated into the prosthesis to aidin combating clinical and sub-clinical infections in a surgical ortrauma wound site.

To promote wound repair and/or tissue growth, one or several growthpromoting factors can be introduced into the tubular prosthesis, e.g.,fibroblast growth factor, platelet derived growth factor, macrophagederived growth factor, alveolar derived growth factor, monocyte derivedgrowth factor, magainin, and so forth. To decrease abrasion, increaselubricity, etc., the prosthesis can be coated with copolymers ofglycolide and lactide and polyethylene oxide, calcium salts such ascalcium stearate, compounds of the Pluronic class, copolymers ofcaprolactone, caprolactone with PEO, polyHEMA, etc. Especiallyadvantageous is a coating of hyaluronic acid with or withoutcross-linking.

Additionally, polypeptides such as Human Growth Factor (HGF) can also becoated upon or impregnated in the prosthesis to promote healing. Theterm "Human Growth Factor" or "HGF" embraces those materials, known inthe literature, which are referred to as such and includes theirbiologically active, closely related derivatives. The HGFs can bederived from naturally occurring sources and are preferably produced byrecombinant DNA techniques. Specifically, any of the HGFs which aremitogenically active and as such effective in stimulating, accelerating,potentiating or otherwise enhancing the wound healing process are usefulherein, e.g., hEGF (urogastrone), TGF-beta, IGF, PDGD, FGF, etc. Theseand other useful HGFs and closely related HGF derivatives, methods bywhich they can be obtained and methods and compositions featuring theuse of HGFs to enhance wound healing are variously disclosed, interalia. in U.S. Pat. Nos. 3,883,497; 3,917,824; 3,948,875; 4,338,397;4,418,691; 4,528,186, 4,621,052; 4,743,679 and 4,717,717; EuropeanPatent Applications 0 046 039; 0 128 733; 0 131 868; 0 136 490; 0 147178; 0 150 572; 0 177 915 and 0 267 015; PCT International ApplicationsWO 83/04030; WO 85/00369; WO 85/01284 and WO 86/02271 and UK PatentApplications GB 2 092 155 A; 2,162,851 A and GB 2 172 890 A, all ofwhich are incorporated by reference herein. Of the known HGFs, hEGF,TGF-beta and IGF are preferred for use in the therapeutic composition ofthis invention.

The HGFs can be introduced with appropriate carrier such as carrierproteins disclosed, e.g., in "Carrier Protein-Based Delivery of ProteinPharmaceuticals", a paper of Biogrowth, Inc., Richmond, Calif.,presented at a symposium held June 12-14, 1989 in Boston, Mass.

EXAMPLE 1

The following illustrates the manufacture of a ligament prosthesis asillustrated in FIG. 5.

A 420 denier composite yarn as illustrated in FIG. 1 was formed from aHytrel 7246 yarn as the core component and a lactide (80 molepercent)-glycolide (20 mole percent) copolymer yarn providing the sheathcomponent.

Six plies of the 420 denier composite yarn were wound onto 32 braiderbobbins. The bobbins were loaded onto a 32 carrier braider to providebraided sheath 31. About one meter of the yarns from the 32 bobbins waspulled manually in parallel to provide a core 32 of 80,640 (420×6 ×32)overall denier. Application of braided sheath 31 also 420×6×32 or 80,640overall denier resulted in ligament prosthesis 37 possessing an overalldenier of 161,280. The stress (force in Newtons)-strain characteristicsof prothesis 37 were measured and compared with the stress-straincharacteristics of a human anterior cruciate ligament as reported inNoyes et al., Journal of Bone and Joint Surgery, Vol. 58-A, No. 8, p.1074, et seq. (Dec. 1976). As shown in the plotted data of FIG. 6, thestress-strain characteristics of prosthesis 37 (continuous line) closelymatched those of the natural tissue (broken line), an altogetherremarkable achievement relative to known connective tissue prostheses.

EXAMPLE 2

The following illustrates manufacture of a tendon augmentation device 40as illustrated in FIG. 7.

A 431 denier composite yarn as illustrated in FIG. 1 was formed from aHytrel 7246 yarn to provide the core component 12, a lactide (80 molepercent)--glycolide (20 mole percent) copolymer yarn to provide theinner sheath component 14, and a lactide (10 mole percent)--glycolide(90 mole percent) copolymer yarn to provide the outer sheath component16.

Six plies of the 431 denier composite yarn were wound onto 16 braiderbobbins. The bobbins were loaded onto a 16 carrier braider to providebraided sections 42 and 43. About 70 mm of the yarn from the 16 braiderbobbins was braided to form one of sections 42 and 43, and then thebraiding was stopped. Then, about 35 mm. of the yarn from the 16 braiderbobbins was pulled manually to form the unbraided center section 41, andthen braiding was continued for another 70 mm of the yarn to form theother of sections 42 and 43. The resulting tendon augmentation device 40had a total denier of 41,376 (431×6×16).

The tendon augmentation device 40 was implanted in a canine kneereplacing the center third of the patellar tendon. Physical testing wascarried out comparing two tendon augmentation devices 40 (TAD-1 andTAD-2) to the center third of the canine patellar tendon (1/3 P.T.)being replaced. More specifically, the stress (force in Newtons)--strain or load-deformation characteristics of devices 40 and thecanine patellar tendon were measured and compared with one another.

As shown in the plotted data of FIG. 12, the responses of both tendonaugmentation devices 40 (TAD 1 and TAD 2) were very similar to the onethird canine patellar tendon. Moreover, tendon augmentation devices 40(TAD 1 and TAD 2) were generally stronger than the replaced caninepatellar tendon which failed when too great a load was applied thereto.

EXAMPLE 3

A composite yarn as illustrated in FIGS. 3 and 4 was fabricated usingHytrel 7246 fibers as the core component 33 and bioabsorbable sheathcomponent fibers 35 of two different chemical compositions: firstbioabsorbable fibers 35' fabricated from an 80 mole percent lactide/20mole percent glycolide copolymer, and second bioabsorbable fibers 35"fabricated from a 10 mole percent lactide/90 mole percent glycolidecopolymer. The first bioabsorbable fibers 35' were formed into yarnbundles, each yarn bundle comprising 12 filaments and having a totaldenier of 24. The second bioabsorbable fibers 35" were also formed intoyarn bundles, each yarn bundle comprising 17 filaments and having atotal denier of 27.

The composite yarn was formed using three Hytrel yarn bundles, eachHytrel yarn bundle comprising 70 filaments, to form a core component 33of approximately 270 denier. The braided sheath component 34 was formedaround the Hytrel core component 33 using an 8 carrier braider, 4carriers each of the first and second bioabsorbable yarn bundles. Thecomposite yarn thus formed exhibited a tensile strength of 3.19grams/denier, and is suitable for use in fabricating a connective tissueprosthesis of the present invention.

What is claimed is:
 1. A connective tissue prosthesis comprising:a) acore made up of a first biocompatible composite yarn extending in alengthwise direction; and b) a sheath surrounding the core, said sheathbeing fabricated from a second biocompatible yarn; the first compositeyarn in said core (a) comprising a non-bioabsorbable core yarn componentsurrounded by an at least semi-bioabsorbable sheath yarn component. 2.The connective tissue prosthesis of claim 1, wherein the secondbiocompatible yarn in said sheath (b) comprises a non-bioabsorbable coreyarn component surrounded by an at least semi-bioabsorbable sheath yarncomponent.
 3. The connective tissue prosthesis of claim 2 wherein thesheath yarn component is bioabsorbable.
 4. The connective tissueprosthesis of claim 1 exhibiting stress-strain characteristicsapproximately those of the natural connective tissue replaced oraugmented by the prosthesis.
 5. The connective tissue prosthesis ofclaim 1 wherein said connective tissue prosthesis is a ligament ortendon prosthesis.
 6. The connective tissue prosthesis of claim 1wherein said connective tissue prosthesis is a human anterior cruciateligament prosthesis.
 7. The connective tissue prosthesis of claim 1 inwhich the core component comprises at least one filament.
 8. Theconnective tissue prosthesis of claim 7 in which the core (a) of theprosthesis comprises multiple composite yarns.
 9. The connective tissueprosthesis of claim 7 wherein the core component comprises multiplefilaments.
 10. The connective tissue prosthesis of claim 1 in which thesheath component comprises at least one filament.
 11. The connectivetissue prosthesis of claim 10 wherein the sheath yarn componentcomprises multiple filaments.
 12. The connective tissue prosthesis ofclaim 1 in which the core component is manufactured from at least onepolymeric material selected from the group consisting of polyethylenehomopolymers, polypropylene homopolymers, ethylene-propylene copolymers,ethylene propylene terpolymers, fluorinated hydrocarbons,fluorosilicones, isobutylenes, isoprenes, polyacrylates, polybutadienes,polyurethanes, and polyether-polyester copolymers.
 13. The connectivetissue prosthesis of claim 1 in which the core component possesses anelongation at break of at least about 30 percent.
 14. The connectivetissue prosthesis of claim 1 in which the sheath component is anabsorbable, relatively inelastic polymeric material derived at least inpart from a monomer selected from the group consisting of glycolic acid,glycolide, lactic acid, lactide, p-dioxanone, trimethylene carbonate,e-caprolactone and hydroxycaproic acid.
 15. The connective tissueprosthesis of claim 1 in which the sheath component is alactide-glycolide copolymer.
 16. The connective tissue prosthesis ofclaim 12 in which the sheath component is a lactide-glycolide copolymercontaining from about 70 to about 90 mole percent lactide units.
 17. Theconnective tissue prosthesis of claim 16 in which the sheath componentis a lactide-glycolide copolymer containing from about 75 to about 85mole percent lactide units.
 18. The connective tissue prosthesis ofclaim 1 wherein the sheath (b) covering the core (a) is at leastpartially woven.
 19. The connective tissue prosthesis of claim 18wherein the sheath (b) is entirely woven.
 20. The connective tissueprosthesis of claim 1 further comprising at least one bioactivesubstance.
 21. The connective tissue prosthesis of claim 1, wherein saidsheath component is helically wound about said core component.
 22. Theconnective tissue prosthesis of claim 21, additionally comprisingasecond sheath component helically wound about said sheath component in adifferent direction.
 23. The connective tissue prosthesis of claim 22,in which said second sheath component is a lactide-glycolide copolymer.24. The connective tissue prosthesis of claim 22, wherein said first andsecond sheath components have different ratios of absorption.
 25. Theconnective tissue prosthesis of claim 1, wherein said sheath componentis braided around said core component.
 26. The connective tissueprosthesis of claim 25, wherein said sheath component comprises aplurality of bioabsorbable fibers, said fibers comprising at least twodifferent chemical compositions.
 27. The connective tissue prosthesis ofclaim 1, wherein said core (a) and sheath (b) together are branched atdiscrete locations to form gaps between branches of said prosthesis. 28.The connective tissue prosthesis of claim 27, wherein a yarn is wrappedabout said sheath (b) at discrete locations to at least temporarilyretain said sheath (b) about said core (a).
 29. The connective tissueprosthesis of claim 28, wherein said wrapping yarn comprises abiocompatible, non-bioabsorbable core yarn component surrounded by a atleast semi-bioabsorbable sheath yarn component.
 30. The connectivetissue prosthesis of claim 29 wherein said sheath component of saidwrapping yarn is bioabsorbable.
 31. The connective tissue prosthesis ofclaim 1 wherein said sheath yarn component is bioabsorbable.
 32. Theconnective tissue prosthesis of claim 1 wherein the sheath (b) coveringthe core (a) is at least partially braided.
 33. The connective tissueprosthesis of claim 32 wherein the sheath (b) is entirely braided. 34.The connective tissue prosthesis of claim 1 wherein the sheath (b)covering the core (a) is at least partially knitted.
 35. The connectivetissue prosthesis of claim 34 wherein the sheath (b) is entirelyknitted.
 36. A connective tissue prosthesis comprising:a tubularcomponent fabricated from composite yarn, said yarn comprising abiocompatible, core yarn component surrounded by a biocompatible, atleast semi-bioabsorbable sheath yarn component.
 37. The connectivetissue prosthesis of claim 36, comprising a center section where saidyarn is unbraided and bordered by sections where said yarn is braided.38. The connective tissue prosthesis of claim 37, additionallycomprisinga helical wrap about said unbraided center section.
 39. Theconnective tissue prosthesis of claim 38, wherein said helical wrap isfabricated from composite yarn comprising a biocompatible,non-bioabsorbable core yarn component surrounded by a biocompatible, atleast semi-absorbable sheath yarn component.
 40. The connective tissueprosthesis of claim 39, wherein said sheath component is bioabsorbable.41. The connective tissue prosthesis of claim 36, additionallycomprisinga threading member attached to an end thereof, said threadingmember comprising a composite yarn which comprises a biocompatible,non-bioabsorbable core yarn component surrounded by a biocompatible, atleast semi-bioabsorbable sheath yarn component.
 42. The connectivetissue prosthesis of claim 41 wherein said sheath component isbioabsorbable.
 43. The connective tissue prosthesis of claim 36 whereinsaid sheath component is bioabsorbable.
 44. Method for manufacturing aconnective tissue prosthesis, comprisingforming said connective tissueprosthesis from a first biocompatible composite yarn comprising anon-bioabsorbable core yarn component surrounded by an at leastsemibioabsorbable sheath yarn component.
 45. The method of claim 44,wherein said connective tissue prosthesis comprises a core and a sheath,said core being at least partially surrounded by said sheath.
 46. Themethod of claim 45, wherein said biocompatible composite yarn forms saidcore.
 47. The method of claim 44, wherein said biocompatible compositeyarn forms said sheath.
 48. The method of claim 44, wherein the sheathis woven about the core.
 49. The method of claim 48, whereinthe sheathis braided from braider bobbins loaded onto a carrier braider, and thecore is pulled through the thus-braided sheath.
 50. The method of claim48 wherein the sheath is braided about the core.
 51. The method of claim44 wherein said sheath component is bioabsorbable.
 52. The method ofclaim 44 wherein the sheath is knitted about the core.
 53. Method formanufacturing a tubular connective tissue prosthesis, comprisingforminga tubular component from composite yarn comprising a biocompatible,non-bioabsorbable core yarn component surrounded by a biocompatible, atleast semi-absorbable sheath yarn component.
 54. The method of claim 53wherein the tubular component is formed by weaving.
 55. The method ofclaim 53 wherein the tubular component is formed by braiding.
 56. Themethod of claim 55, wherein the tubular component is braided frombraider bobbins loaded onto a carrier braider.
 57. The method of claim53 wherein the tubular component is formed by knitting.
 58. The methodof claim 53 wherein the sheath component is bioabsorbable.